[Federal Register Volume 59, Number 166 (Monday, August 29, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-21278]


[[Page Unknown]]

[Federal Register: August 29, 1994]


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Part IX





Department of Health and Human Services





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Food and Drug Administration



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21 CFR Part 589



Substances Prohibited From Use in Animal Food or Feed; Proposed Rule

Bovine-Derived Materials; Agenda Letters to Manufacturers of FDA-
Regulated Products; Notice
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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 589

[Docket No. 93N-0467]

 

Substances Prohibited From Use in Animal Food or Feed; Specified 
Offal From Adult Sheep and Goats Prohibited in Ruminant Feed; Scrapie

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) proposes to declare 
that specified offal from adult (more than 12 months of age) sheep and 
goats is not generally recognized as safe (GRAS) for use in ruminant 
feed and is an unapproved food additive when added to ruminant feed. 
Accordingly, in the absence of an approved food additive regulation or 
investigational exemption, the use in ruminant feed of ingredients 
containing specified offal from adult sheep or goats will cause the 
feeds to be considered adulterated within the meaning of the Federal 
Food, Drug, and Cosmetic Act (the act). FDA is proposing this action 
because the specified offal may contain the agent that causes scrapie, 
a transmissible spongiform encephalopathy (TSE) of sheep and goats. In 
the United Kingdom scrapie has been epidemiologically associated with 
the occurrence of bovine spongiform encephalopathy (BSE), another TSE. 
Because FDA cannot positively rule out a direct association between 
scrapie, BSE and human TSE's, FDA is proposing this action to protect 
the health of animals and humans.

DATES: Written comments by November 14, 1994. FDA is proposing that any 
final rule that may issue based upon this proposal become effective 30 
days after its publication in the Federal Register).

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, rm. 1-23, 12420 Parklawn Dr., 
Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: John P. Honstead, Center For 
Veterinary Medicine (HFV-222), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 301-594-1728.

SUPPLEMENTARY INFORMATION:

I. Background

    Processed tissues from sheep and goats are used as ingredients in 
animal feeds. These products are derived from slaughter byproducts 
(slaughter inedibles) and dead, dying, diseased, and disabled (4-D) 
animals. The slaughter inedibles include certain offal (brain, spinal 
cord, spleen, thymus, tonsil, lymph nodes, or intestines) that is 
subject of this proposed rule. Four-D animals also contain these 
designated materials. Such materials are designated ``specified 
offals'' in this proposed rule.
    The Association of American Feed Control Officials (AAFCO) has 
recognized and defined several animal products as feed ingredients in 
its official publication (Ref. 1). Products which are likely to contain 
specified offal include, dried meat solubles, glandular meal, meat 
meal, meat and bone meal, animal byproduct meal, meat meal tankage, 
animal digest, bone ash, bone charcoal, spent bone charcoal, cooked 
bone meal, and bone phosphate.

A. Processing Animal Tissues for Feed Ingredients

    Generally, feed ingredients from slaughter byproducts and 4-D 
animals are processed by rendering. Rendering involves cooking the 
slaughter byproducts or the whole carcasses of 4-D animals at 240 to 
290  deg.F for 20 minutes to 3 hours to separate oils, fats, and 
protein (Ref. 2). These rendered products are used as ingredients to 
provide essential nutrients in animal feed. However, there are 
processes other than rendering, such as drying, in which slaughter 
byproducts are manufactured into feed ingredients.
    Because of the prolonged application of heat and the associated 
transformation of the tissues, rendering is generally regarded by FDA 
as a process that ensures that the ingredients pose no threat of 
disease to animals or to the health of humans who consume animal 
products such as meat, milk, and eggs. In its role as regulator of 
rendering practices, FDA has focused on the efficacy of a facility's 
rendering process in the prevention of disease transmission and the 
prevention of contamination of the finished products (Ref. 3). FDA has 
no previous evidence of a human or animal health TSE hazard or any 
other health hazard associated with the feeding of adequately rendered 
ingredients to animals. Processed animal byproducts have a long history 
of safe use in the United States as a source of nutrients for animals.
    However, the agent responsible for the transmission of BSE and 
related TSE diseases is not well characterized. It is believed to be a 
cattle variant of the sheep scrapie agent (Refs. 4 and 5). As explained 
more fully below, epidemiological evidence from the United Kingdom 
suggests that a disease agent contained in sheep may have survived the 
rendering process to cause BSE in cattle. This is the first reported 
instance in which it is suspected that a disease agent survived 
rendering.
    The occurrence of BSE in cattle has not been shown to cause a TSE 
disease in humans (Ref. 6). On the other hand, the possibility of a 
causal relationship has not been disproved. BSE has not been diagnosed 
in cattle in the United States (Ref. 7). However, sheep scrapie is 
present in the United States. Accordingly, the agency believes that the 
potential implications for humans as well as animal health require 
regulatory action to minimize the possibility for the introduction of 
the disease into U.S. cattle. For reasons described more fully below, 
FDA is proposing that any feed ingredient that contains specified offal 
from adult sheep or goats is a food additive when added to the feed of 
ruminants.

B. Transmissible Spongiform Encephalopathies (TSE's)

    TSE's are progressively degenerative central nervous system (CNS) 
diseases of man and animals that are characterized by a long incubation 
period, a relatively short clinical course of neurological signs, and a 
100-percent mortality (Ref. 8). TSE's are believed to be caused by 
abnormal isoform neuronal membrane proteins which contain no detectable 
nucleic acids, are resistant to most methods of sterilization, and 
survive severe environmental conditions such as 360  deg.C dry heat 
(Refs. 6 and 9). The agent, however, is not generally believed to be a 
virus, but rather a protein devoid of nucleic acid components. Nucleic 
acid components are characteristic of other living microorganisms. 
These proteins have been termed prions, and are abnormal forms of 
proteins already present in all animals (Refs. 10 and 11). In most 
cases the natural route of exposure to the TSE agent is suspected to be 
oral, although genetic disposition is known to play a role in some 
cases of sheep scrapie and human TSE diseases including Creutzfeldt-
Jakob disease, and Gerstmann-Straussler Syndrome (Ref. 12).
    Antemortem diagnostic tests for the detection of TSE do not exist. 
Postmortem tests are required to confirm suspected TSE cases. The 
observation of histopathological changes in the brain, such as 
vacuolization of the brainstem, are positive indicators (Ref. 13). 
Other diagnostic tests available are immunohistochemical staining and 
immunoblotting the abnormal protein (Ref. 14). Detection and titration 
of the TSE agent can also be accomplished by intracerebral inoculation 
in mice or hamsters with a brain homogenate from a suspected animal. 
After an appropriate incubation period, the brain of the laboratory 
animal is examined for histopathological changes characteristic of TSE 
(Ref. 15).
1. Sheep Scrapie
    Scrapie is a slowly progressive, transmissible disease of the CNS 
in sheep and goats. Scrapie is characterized by a prolonged incubation 
period averaging 2 years, followed by a clinical course of 2 to 6 
months when the animal exhibits sensory and motor malfunction, 
depression, and death. The agent presumably moves from infected to 
susceptible animals by direct or indirect contact and enters through 
the gastrointestinal tract. Consequently, its spread is both vertical 
(mother to offspring in utero) (Ref. 16) and horizontal (direct 
contact) between sheep (Ref. 15). Early signs of scrapie include subtle 
changes in behavior or temperament which may be followed by scratching 
and rubbing against fixed objects. Other signs include loss of 
coordination, weight loss despite a good appetite, biting of feet and 
limbs, tremor around head and neck, and unusual walking habits (Ref. 
17). Since there is no detectable immune response to scrapie, diagnosis 
of scrapie in live sheep is possible only when clinical signs are 
evident and must be confirmed by histopathology at postmortem (Ref. 
14).
    The scrapie agent may be identified in lymphatic tissue (spleen, 
thymus, tonsil, and lymph nodes) in sheep with preclinical infections; 
however, in clinically affected adult sheep, the agent is identified in 
the intestines, nervous tissues (brain and spinal cord), and lymphatic 
tissues (Ref. 15). The brain has been shown to contain by far the 
highest scrapie infectivity of any body tissue.
    Scrapie is known to have existed in Britain, Ireland, France, and 
Germany for over 200 years. It has been observed in the United States 
and Canada for about 50 years. The first case of scrapie in the United 
States was diagnosed in Michigan in 1947. From 1947 through January 
1993, approximately 653 flocks have been diagnosed with scrapie (Ref. 
18).
    In 1993, there were estimated to be a total of 11 million sheep in 
112,000 flocks in the United States. At the present time, there are 108 
known scrapie-infected flocks (flocks with sheep diagnosed with 
scrapie) containing a total of 7,430 sheep, and there are 13 known 
scrapie-source flocks (flocks to which scrapie-infected sheep were 
traced) containing a total of 3,418 sheep (Ref. 19).
    In the absence of an antemortem diagnostic test, it is not possible 
to establish with absolute certainty that a flock is free of scrapie 
infection. Moreover, lack of reporting, the long incubation period, and 
open range husbandry practices in the western United States make it 
difficult to detect classical clinical signs and accurately monitor 
scrapie in the United States.
2. Bovine Spongiform Encephalopathy (BSE)
    BSE was first recognized as a new cattle disease by researchers at 
the Central Veterinary Laboratory of the British Ministry of 
Agriculture, Fisheries, and Foods at Weybridge, England in November 
1986. In retrospect, the literature indicates that the first clinical 
case of BSE may have been observed as early as April 1985 (Ref. 20). As 
of September 1993, there have been more than 100,000 confirmed cases of 
BSE in England, Scotland, and Wales. In the United Kingdom, 44 percent 
of the dairy herds and 9 percent of the beef herds are infected (Ref. 
21). BSE has also been reported in Northern Ireland, the Republic of 
Ireland, Switzerland, France, Oman, and the Falkland Islands (Ref. 22).
    BSE is a transmissible, slowly progressive, degenerative disease of 
the CNS of adult cattle. This disease has a prolonged incubation period 
in cattle following oral exposure (2 to 8 years) and is always fatal. 
BSE is characterized by abnormalities of behavior, sensation, posture, 
and gait. These signs are similar to those seen in sheep that are 
infected with scrapie. BSE is associated with spongiform lesions in the 
gray matter neuropil of the brainstem and neuronal vacuolization (Ref. 
21). The clinical signs usually begin with changes in animal behavior 
that are suggestive of apprehension, anxiety, and fear. There is 
increased reaction to sound and touch. A swaying gait is sometimes 
coupled with high stepping of the feet and is most evident in the hind 
limbs. Changes in the normal behavior of the individual cow may also 
include separation from the rest of the herd while at pasture, 
disorientation, or excessive licking of the nose or flanks (Ref. 23). 
The most common history given by the herdsman was nervousness or 
altered behavior or temperament, weakness associated with pelvic limb 
ataxia, paresis, and loss of body weight (Ref. 24).
    In some animals there are few gross pathological changes at 
necropsy associated with BSE other than the loss of body weight. 
However, postmortem histopathology of BSE distinguish it from other 
neurological disorders (Refs. 25 and 26).
3. Other Animal TSE's
    Transmissible mink encephalopathy (TME) is a mink disease with 
clinical signs and brain lesions similar to those of sheep infected 
with scrapie. The development of TME on a mink farm that reportedly fed 
only cattle byproducts has led some to believe that BSE exists at a low 
level in the United States (Ref. 27). TME is a rare disease in the 
United States, with only 5 outbreaks (involving 11 mink farms) reported 
in the last 50 years. Based on available evidence, the U.S. Department 
of Agriculture (USDA) has concluded that the byproducts from United 
States cattle are unlikely to have caused the TME outbreak on the mink 
farm (Ref. 28).
    Other animals have TSE's with typical characteristics of long 
incubation, neurological degeneration, and a 100-percent death rate. 
These include elk and deer (Refs. 29 and 30), zoo ruminants (Refs. 31, 
32, and 33), and domestic cats (Refs. 34 and 35).

C. The Association Between Scrapie and BSE

    Epidemiological studies of the outbreak of BSE in the United 
Kingdom, including a computer simulation of the BSE epidemic, have 
characterized it as an extended common-source epidemic. Each case has 
been considered a primary case resulting from exposure to a single 
common source of infection. It is believed that rendered feed 
ingredients contaminated with sheep scrapie and BSE agents served as 
the common source of infection. One study demonstrated that meat and 
bone meal could be incorporated into the cattle feed in sufficient 
quantity to initiate clinical BSE in some of the animals that consumed 
the feed (Ref. 36). Thus far, other research has not confirmed that the 
feeding of scrapie-infected feed ingredients to cattle produces BSE. 
Therefore, the theory that BSE evolved naturally in cattle has not been 
ruled out (Ref. 37). Furthermore, the United Kingdom studies suggest 
that the spread of BSE appeared to have been exacerbated by the 
practice of feeding ingredients from rendered BSE-infected cattle to 
calves, a practice that was subsequently banned. Incomplete immediate 
compliance with the feeding ban may account for the fact that some 
calves born after the ban continue to be infected with BSE has 
complicated any theory of vertical transmission of the disease. 
Maternal transmission has been documented, but at a rate insufficient 
to maintain the epidemic (Ref. 38).
    Investigators have identified major risk factors that apparently 
contributed to the emergence of BSE epidemic in the United Kingdom 
(Refs. 39 to 42). These include:
    (1) A large sheep population, relative to cattle population;
    (2) A high scrapie incidence rate;
    (3) The practice of feeding rendered products from BSE-infected 
cattle to young cattle at high amounts (up to 4 percent of the diet);
    (4) The feeding of greaves. In the United Kingdom, whole dead 
animals were processed as a source of tallow. The remaining unextracted 
bone and protein solids, termed ``greaves,'' were used as dairy calf 
feed. The greaves may have contained the BSE agent. This practice is 
not followed in the United States and has stopped in the United 
Kingdom; and
    (5) Changes in the rendering process. In 1981-1982, the rendering 
industry in the United Kingdom reduced the use of hydrocarbon solvent 
extraction in the rendering process (Ref. 43). The United States 
rendering industry had taken this step in the 1970's. The appearance of 
BSE in the United Kingdom approximately 3 years after the change in the 
rendering process is consistent with the 2- to 8-year incubation period 
of BSE. The epidemiological evidence has suggested that changes in the 
solvent extraction process was the major factor responsible for 
initiating a BSE epidemic in the United Kingdom. Furthermore, 
laboratory tests based on intracerebral injection studies in rodents 
indicated that the hydrocarbon extraction method inactivated the 
causative agent while the heat method did not inactivate the scrapie-
like agent present in rendered animal byproducts (Refs. 13 and 40). The 
heat extraction method is the most common rendering process currently 
in use world wide.

D. Historical Efforts To Control BSE

1. United Kingdom Regulatory Actions
    Regulatory controls taken to manage the BSE epidemic in the United 
Kingdom and to address public health concern include: (1) An action in 
June 1988 to make the disease reportable; (2) a ban in July 1988 on the 
feeding of ruminant-derived protein supplements to other ruminants; (3) 
an order in August 1988 for the compulsory slaughter and incineration 
of BSE suspect cattle; (4) a ban in November 1988 on the human 
consumption of specified offals (including brain, spinal cord, thymus, 
spleen, tonsils, and intestines) of ruminants; and (5) a ban in 
September 1990 of feeding any ingredient containing specified offals to 
all pet and farm animals.
    The Office Internationale Epizootics (OIE) has supported the U.K. 
ban on the use of specified offals and has recommended that the same 
action be taken in other countries with a high incidence of the disease 
(Ref. 44). OIE has recommended that British manufacturers of human and 
animal drugs and biologics not use source material from BSE-positive 
countries.
2. United States Regulatory Actions
    The USDA Animal and Plant Health Inspection Service (APHIS) has had 
a scrapie control program in effect since 1952. This program has been 
responsible for the relatively low incidence of the disease in the 
United States. In December 1991, APHIS placed a ban on importation of 
certain products of ruminant origin from countries known to have BSE 
(56 FR 63865, December 6, 1991). These products include meat-and-bone 
meal, bone meal, blood meal, offal, fat, and glands. In addition to 
prohibiting the materials listed above, the regulation requires that 
imported meat for human or animal consumption from the ruminants in the 
Bovidae family (e.g., cattle) be deboned, with visible lymphatic and 
nervous tissue removed; that it be obtained from animals which have 
undergone a veterinary examination prior to slaughter; and that it be 
obtained from ruminants which have not been in any country in which BSE 
has been reported during a period of time when that country permitted 
the use of ruminant protein in ruminant feed.
    In addition to these import restrictions, APHIS has increased its 
surveillance efforts to verify that the United States is free of BSE 
and to detect the disease should it be introduced into the United 
States. APHIS is tracing the movement and current health status of 459 
cattle that were imported from United Kingdom between 1981 and 1989.
    Due to concerns about BSE in the United States, USDA has 
implemented several programs to monitor United States cattle. 
Pathologists at Iowa State University and the National Veterinary 
Service Laboratories (NVSL) of APHIS, USDA, are examining bovine brains 
submitted to NVSL from the following sources: (1) Foreign animal 
disease investigations where suspected encephalitic conditions in 
cattle are reported; (2) Centers for Disease Control laboratories 
(specimens that were found negative for rabies); (3) the USDA Food 
Safety and Inspection Service (specimens from nonambulatory, commonly 
called downer cows); and (4) veterinary diagnostic laboratories in the 
United States. Between 1989 and October 1993, a total of 1,153 bovine 
brains have been examined and none of these specimens contained lesions 
with the characteristics and distribution typical for BSE (Ref. 45). 
This program is ongoing. Data on the incidence of cattle in the United 
States showing clinical symptoms of CNS disease that are similar to 
clinical symptoms of BSE have shown no increase during the past 5 years 
(Ref. 46).
    To decrease further the incidence of scrapie and the threat of BSE 
in the United States, APHIS, in 1992, initiated a voluntary 
certification program for sheep (57 FR 58132, December 9, 1992). Flocks 
that have not had a diagnosed case of scrapie within 5 years, or a case 
traced back to the flock in that period, may apply for APHIS 
certification and be officially identified as such. This new control 
effort provides a mechanism to recognize flocks as scrapie-free in the 
absence of a live animal diagnostic test.
3. Voluntary Ban by Renderers
    In 1989, the National Renderers Association (NRA) and the Animal 
Protein Producers Industry (APPI) recommended to its members that they 
stop rendering adult sheep or sheep offal for sale as meat and bone 
meal for inclusion in cattle feed (Ref. 47). Following adoption of the 
voluntary ban, the FDA carried out a survey of current practices in the 
United States for rendering or otherwise disposing of adult sheep 
carcasses and parts, specifically head, brain, and spinal cord. Limited 
inspections of rendering plants were conducted to: (1) Assess 
compliance by United States renderers with the industry imposed 
voluntary ban on rendering adult sheep for cattle feed; (2) identify 
rendering plant practices concerning adult sheep; and (3) determine if 
rendered adult sheep protein byproducts were being sold or labeled for 
use as feed or feed components for cattle. Of the 19 plants surveyed, 
15 rendered carcasses or offal of adult sheep. These 15 plants 
processed more than 85 percent of the adult sheep rendered in the 
United States. Eleven of the 15 rendered carcasses of adult sheep with 
heads, 7 of the 15 rendered sheep carcasses separately from other 
species, 6 of the 15 maintained meat and bone meal from adult sheep 
separate from meat and bone meal from other species, and 4 of the 15 
rendered sheep that had died of causes other than slaughter. Six of the 
11 renderers processing adult sheep with heads had sold meat and bone 
meal to manufacturers of cattle feed; thus, the rendering industry's 
voluntary ban was not fully implemented at the time of the survey (Ref. 
48).

II. The Regulatory Issues

    The term ``food'' as defined in the act includes animal feed. 
Section 201(f) of the act (21 U.S.C. 321(f)) defines food as ``articles 
used for food or drink for man or other animals'' and ``articles used 
for components of any such article.'' Furthermore, any substance whose 
intended use results or may reasonably be expected to result in its 
becoming a component of food is a food additive unless, among other 
things, it is GRAS or is the subject of a prior sanction. Section 
402(a)(2)(C) of the act (21 U.S.C. 342(a)(2)(C)) deems food adulterated 
``if it is, or it bears or contains, any food additive which is unsafe 
within the meaning of section 409 * * * .'' Under section 409(a)(2) of 
the act (21 U.S.C. 348(a)(2)), a food additive is unsafe unless a food 
additive regulation or an exemption is in effect with respect to its 
use or its intended use.
    A food additive regulation is established by the submission and 
approval of a food additive petition, as provided in 21 CFR 571.1, or 
on FDA's initiative as provided in Sec. 570.38 (21 CFR 570.38). The 
Commissioner of Food and Drugs (the Commissioner), on his own 
initiative or at the request of an interested party, may propose to 
determine that a substance intended for use in animal feed is not GRAS 
and is a food additive subject to section 409 of the act and 
Sec. 570.38. Subsequent to the publication of such a proposal and after 
consideration of public comments, the Commissioner may issue a final 
rule declaring the substance to be a food additive and require 
discontinuation of its use except when used in compliance with a food 
additive regulation.

A. GRAS Determination

    A determination that a substance added directly or indirectly to a 
food is GRAS is generally based on specific information regarding the 
composition of the substance, its use, method of preparation, methods 
for detecting its presence in food, and information about its 
functionality in food (21 CFR 570.35) as determined by experts 
qualified by scientific training and experience to evaluate the safety 
of such a substance. A substance added to food becomes GRAS as the 
result of a common understanding about the substance throughout the 
scientific community familiar with safety of such substances. The basis 
of expert views may be either scientific procedures, or, in the case of 
a substance used in food prior to January 1, 1958, experience based on 
common use in food (Sec. 570.30(a) (21 CFR 570.30(a))).
    General recognition of safety through experience based on common 
use in food prior to January 1, 1958, may be determined without the 
quantity or quality of scientific studies required for the approval of 
a food additive regulation. However, substances that are GRAS based on 
such use must be currently recognized as safe based on their pre-1958 
use. (See United States v. Naremco, 553 F.2d 1138 (8th Cir. 1977); 
compare United States v. Western Serum, 666 F.2d 335 (9th Cir. 1982).) 
A recognition of safety through common use is ordinarily to be based on 
generally available data and information (Sec. 570.30(c)). An 
ingredient that was not in common use in food prior to January 1, 1958, 
may achieve general recognition of safety only through scientific 
procedures.
    General recognition of safety based upon scientific procedures 
requires the same quantity and quality of scientific evidence as is 
required to obtain approval of a food additive regulation for the 
ingredient (Sec. 570.30(b); United States v. Naremco, supra, 553 F.2d 
at 1143). A substance is not GRAS if there is a genuine dispute among 
experts as to its recognition (An Article of Drug * * * Furestrol 
Vaginal Suppositories, 251 F. Supp. 1307 (N.D. Ga. 1968), aff'd 415 
F.2d 390 (5th Cir. 1969)). Further, general recognition of safety 
through scientific procedures must be based upon published studies 
(United States v. Articles of Food and Drug Colitrol 80 Medicated, 372 
F. Supp. 915 (N.D. Ga. 1974), aff'd, 518 F.2d 743, 747 (5th Cir. 
1975)), so that the results are generally available to experts. It is 
not enough, in attempting to establish that a substance is GRAS, to 
establish that there is an absence of scientific studies that 
demonstrate the substance to be unsafe; there must be studies that show 
the substance to be safe (United States v. An Article of Food, 752 F.2d 
11, 15 (1st Cir. 1985)).
    Conversely, a substance may be ineligible for GRAS status if 
studies show that the substance is, or may be, unsafe. This is true 
whether the studies are published or unpublished (50 FR 27294 at 27296, 
July 2, 1985). If there are studies that tend to support a finding that 
a particular substance is GRAS, but also studies that tend to support a 
contrary position, the conflict in the studies, just as a conflict in 
expert opinion, may prevent the general recognition of the safe use of 
the substance.

B. Food Additive Status of Specified Offal From Adult Sheep and Goats

    The agency recognizes that the processed slaughter byproducts and 
4-D adult sheep and goats have a long history of use in animal feeds 
without known adverse effects. However, the evidence for the 
development of a new pattern of disease transmission now indicates that 
these ingredients can no longer be categorically regarded as safe. The 
agency believes that the epidemiological evidence linking the 
occurrence of BSE in ruminants with the feed ingredients containing 
specified offal from adult sheep and goats precludes any claim of 
reliance upon a general recognition of safety as a sufficient basis for 
the continued use of these specified offals in food.
    The agency reached this conclusion in light of the findings 
regarding a possible mechanism for the transmission of BSE to ruminants 
as a result of feed ingredients containing specified offal from 
scrapie-infected adult sheep and goats, as discussed in section I.B. of 
this document. FDA cannot determine what level of feed ingredients from 
processed adult sheep and goat products, if any, is safe in ruminant 
feed.
    A search of the scientific literature did not reveal information 
that would provide a basis for the GRAS status of feed ingredients 
derived from processed adult sheep or goat slaughter byproducts. Nor is 
the agency aware of a prior sanction for any feed products that contain 
these products.
    In view of the above, FDA has preliminarily concluded that the 
addition of specified offal to ruminant feed constitutes, in light of 
the epidemiological evidence about BSE, the use of an unapproved food 
additive. A regulation for the use of processed adult sheep- and goat-
specified offal in ruminant feed is not in effect. Therefore, it is 
FDA's preliminary conclusion that any ruminant feed that contains such 
an ingredient is adulterated. Accordingly, FDA is proposing to list 
specified offal from sheep or goat over 12 months of age in 21 CFR Part 
589--Substances Prohibited From Use in Animal Food or Feed.

III. Description of the Proposed Rule

    The proposed rule would prohibit use of any feed ingredient 
containing specified offal from sheep and goats over 12 months of age 
in ruminant feed. Specified offal is defined as any tissue from the 
brain, spinal cord, spleen, thymus, tonsil, lymph nodes, or intestines 
(duodenum to anus, inclusive) of sheep or goats, or any processed 
product that is reasonably expected to contain specified offal.

A. Exclusion of Sheep and Goats Under 12 Months

    The exclusion of animal tissues from young animals is based on the 
observation that sheep less than 12 months old rarely exhibit clinical 
symptoms of scrapie, although a few cases have been reported in sheep 
as young as 7 months (Ref. 49). Historically, APHIS scrapie regulations 
and indemnity programs have used a 12-month cutoff for eligible adult 
sheep. The NRA and APPI voluntary ban on rendering sheep for cattle 
feed also used a 12-month cutoff for high-risk sheep. The median age of 
onset of clinical scrapie is 3 1/2 years, and 82 percent of sheep died 
of scrapie between the ages of 2 and 5 years (Ref. 14). Based on all of 
the available data, the agency has tentatively concluded that any 
ruminant feed ingredients derived from sheep and goats under 12 months 
of age represent a minimal risk of exposure to the scrapie agent. The 
agency invites comment on the exclusion of sheep and goats less than 12 
months old from the proposed ban.

B. Inclusion of Goats

    Scrapie is a disease which may affect both sheep and goats. 
However, in the United States only four cases have been diagnosed in 
goats (Ref. 18). All four goats were raised with sheep flocks in which 
sheep scrapie was present. Even though the number of reported cases in 
goats is low, there may be a substantial number of cases undiagnosed 
and unreported. Because of the possibility of unreported scrapies in 
goats, FDA is proposing to include adult goats in this regulation. The 
agency invites comment on the inclusion of adult goats in the proposed 
rule.

C. Exemption of APHIS-Certified Flocks

    FDA has considered exempting adult sheep and goats from one or more 
categories of APHIS-certified flocks from this prohibition. This would 
provide added incentive for producers to enroll in the certification 
program. On the other hand, such exclusion could cause enforcement 
difficulties, because of the need for separate identification of sheep 
and goats from certified flocks. The agency has tentatively decided not 
to exempt specified offal from certified flocks. However, the agency 
invites comment on this issue, and will consider adding the exclusion 
to the final rule.

D. Summary of the Basis for FDA Regulation

    Epidemiological studies in the United Kingdom indicate that feeding 
calves products containing feed ingredients processed from sheep 
infected with scrapie initiated BSE in cattle. Scrapie-infected sheep 
flocks are present in the United States, and the scrapie agent is known 
to survive the rendering procedures currently in use. A 1992 FDA survey 
showed that renderers have not complied fully with their voluntary ban 
on selling rendered adult sheep products for use in cattle feed. Thus, 
to help prevent a BSE outbreak in the United States, regulation and 
enforcement are needed to ensure that feed ingredients made from 
specified offal derived from processed slaughter inedibles and 
carcasses of adult sheep and goats are not used in ruminant feed.
    The agency has considered whether to impose a broader ruminant-to-
ruminant ban, i.e., a restriction on feeding to cattle and other 
ruminants the specified offal from all ruminants rather than just from 
sheep and goats. The purpose of a ruminant-to-ruminant ban would be to 
prevent the spread of BSE between cows. Since no case of BSE has been 
documented in the United States under the extensive monitoring 
described in section I.D.2. of this document, the agency has determined 
that a broader ruminant-to-ruminant ban is not warranted at this time. 
If, and when, BSE is documented in the United States, the agency will 
reevaluate this determination.
    While controlled scientific studies have not established a 
definitive association between scrapie and BSE, epidemiologic studies 
have linked the feeding of scrapie infected feedstuffs to cattle with 
the occurrence of BSE. Therefore, the agency believes the action set 
forth in this proposal is warranted to minimize the potential risk that 
scrapie from sheep and goats may result in the introduction of BSE to 
cattle in the United States in light of the impact that BSE may have on 
animal and human health. The agency's proposal is consistent with 
action taken by APHIS, USDA to reduce the risk that BSE will occur in 
the United States by eliminating scrapie from U.S. sheep.

IV. Environmental Impact

    FDA has carefully considered the potential environmental effects of 
this proposed rule and has concluded that the proposed rule will not 
have a significant impact on the human environment and that an 
environmental impact statement is not required. FDA's finding of no 
significant impact (FONSI) and the evidence supporting that finding, 
contained in an environmental assessment (EA) prepared under 21 CFR 
25.31, may be seen in the Dockets Management Branch (address above) 
between 9 a.m. and 4 p.m., Monday through Friday. FDA invites comments 
and submission of data concerning the EA and FONSI.

V. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354). 
Executive Order 12866 directs agencies to assess all costs and benefits 
of available regulatory alternatives and, when regulation is necessary, 
to select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The agency believes that 
this proposed rule is consistent with the regulatory philosophy and 
principles identified in the Executive Order. In addition, the proposed 
rule is not a significant regulatory action as defined by the Executive 
Order and so is not subject to review under the Executive Order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Based on a study conducted for the agency by the 
Eastern Research Group (ERG), a private consulting firm, FDA has 
determined the annual costs of the proposed regulation to the affected 
industries. FDA estimated the annual loss of revenues to the sheep 
ranching and goat ranching industries to be $2,400,000 and $1,500,000, 
respectively. FDA further estimated the decrease in profits to the 
slaughtering and rendering industries due to the decline in 
slaughtering and rendering activities to be $356,000 per year. 
Additional disposal costs to slaughterers are estimated to range from 
$111,000 to $166,000 per year. The effects of the proposed regulation 
on feed manufacturers are believed to be negligible. Therefore, the 
agency certifies that the proposed rule will not have a significant 
economic impact on a substantial number of small entities, and, under 
the Regulatory Flexibility Act, no further analysis is required.
    A copy of the ERG report supporting these determinations is on file 
with the Dockets Management Branch (address above).

VI. References

    The following references have been placed on display in the Dockets 
Management Branch (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
    1. AAFCO, ``Official Publication 1993 Association of American 
Feed Control Officials,'' pp. 128-137, 1993.
    2. John, R. E., ``National Renderers Association Feed Safety 
Assurance Efforts,'' in a symposium, ``Feed Quality Assurance, A 
System-Wide Approach,'' p. 67, 1990.
    3. FDA, Compliance Policy Guide 7126.24, ``Rendered Animal Feed 
Ingredients,'' 1980.
    4. Hope, J. et al., ``Fibrils From Brains of Cows With New 
Cattle Disease Contain Scrapie-Associated Protein,'' Nature, 
336:390, 1988.
    5. Kimberlin, R. H., ``Transmissible Encephalopathies in 
Animals,'' Canadian Journal of Veterinary Research, 54:30-37, 1990.
    6. Taylor, D. M., ``Inactivation of BSE Agent,'' in ``Symposium 
on Virological Aspects of the Safety of Biological Products,'' 1990.
    7. USDA, ``Bovine Spongiform Encephalopathy Surveillance in the 
United States,'' 1993.
    8. McCaskey, P. C., ``Spongiform Encephalopathy in Other 
Species,'' Toxicology Forum, 185-195, 1991.
    9. Brown, P., P. P. Liberski, A. Wolff, and D. C. Gajdusek, 
``Resistance of Scrapie Infectivity to Steam Autoclaving After 
Formaldehyde Fixation and Limited Survival After Ashing at 360 
deg.C: Practical and Theoretical Implications,'' Journal of 
Infectious Diseases, 161:467-472, 1989.
    10. Prusiner, S. B. et al., ``Immunologic and Molecular Biologic 
Studies of Prion Proteins in Bovine Spongiform Encephalopathy,'' 
Journal of Infections Diseases, 167:602-613, 1993.
    11. Stahl, N. and S. B. Prusiner, ``Prions and Prion Proteins,'' 
FASEB Journal, 5:2799-2807, 1991.
    12. Hsiao, K., ``Mutation of the Prion Protein in Libyan Jews 
With Creutzfeldt-Jakob Disease,'' New England Journal of Medicine, 
324:1091-1097, 1991.
    13. Kimberlin, R. H., ``Bovine Spongiform Encephalopathy,'' 
Scientific and Technical Review, 11(2):347-390, 1992.
    14. Detweiler, L. A., ``Scrapie,'' Revue Scientifique et 
Technique, Office Internationale Epizootics, 11(2):491-537, 1992.
    15. Hadlow, W. J., R. C. Kennedy, and R. E. Race, ``Natural 
Infection of Suffolk Sheep With Scrapie Virus,'' Journal of 
Infectious Diseases, 146:657, 1982.
    16. Foster, J. D. et al., ``Studies on Maternal Transmission of 
Scrapie in Sheep,'' Veterinary Record, 130:341-343, 1992.
    17. Kimberling, C. V., ``Jensen and Swift's Diseases of Sheep,'' 
Lea and Febiger, pp. 336-340, Philadelphia, 1988.
    18. USDA, APHIS, Veterinary Services, ``Fact Sheet: Scrapie,'' 
June 1993.
    19. Lang, J., ``Scrapie Progress Report,'' 1(1):1-4, March 15, 
1993.
    20. Wells, G. A. H., A. C. Scott, and C. T. Johnson, et al., ``A 
Novel Progressive Spongiform Encephalopathy in Cattle,'' Veterinary 
Record, 121:419-420, 1987.
    21. Bradley, R., ``Editorial: Bovine Spongiform Encephalopathy: 
The Need for Knowledge, Balance, Patience, and Action,'' Journal of 
Pathology, 160:283-285, 1990.
    22. Denny, O, A. Doherty, B. Hornlimann, and J. Wilesmith, 
``Bovine Spongiform Encephalopathy,'' in ``DxMonitor,'' Summer 1993.
    23. Hueston, W., ``Clinical Signs of BSE,'' in ``Animal Health 
Insight,'' Summer:4, 1991.
    24. Wilesmith, J. W., G. A. H. Wells, M. P. Cranwell, and J. B. 
M. Ryan, ``Bovine Spongiform Encephalopathy: Epidemiological 
Studies,'' Veterinary Record, 123:638-644, 1988.
    25. Wells, G. A. H. et al., ``Bovine Spongiform Encephalopathy: 
Diagnostic Significance of Vacuolar Changes in Selected Nuclei of 
the Medulla Oblongata,'' Veterinary Record, 125:521-524, 1989.
    26. Davis, A. J., A. L. Jenny, and L. D. Miller, ``Diagnostic 
Characteristics of Bovine Spongiform Encephalopathy,'' Journal of 
Veterinary Diagnostic Investigations, 3:266-271, 1991.
    27. Marsh, R. F. and R. A. Bessen, ``Epidemiologic and 
Experimental Studies on Transmissible Mink Encephalopathy,'' in 
``Transmissible Spongiform Encephalopathy--Impact on Animal and 
Human Health,'' 80:105-112, 1993.
    28. Bridges, V., A. Bleem, and K. Walker, ``Risk of 
Transmissible Mink Encephalopathy in the United States,'' in 
``Animal Health Insight,'' pp. 7-14, USDA Veterinary Services, Fall 
1991.
    29. Williams, E. S. and S. Young, ``Neuropathology of Chronic 
Wasting Disease of Mule Deer and Elk,'' Veterinary Pathology, 30:36-
45, 1993.
    30. Williams, E. S. and S. Young, ``Chronic Wasting Disease of 
Captive Mule Deer: A Spongiform Encephalopathy,'' Journal of 
Wildlife Diseases, 16-1:89-98, 1980.
    31. Fleetwood, A. J. and C. W. Furley, ``Spongiform 
Encephalopathy in an Eland,'' Veterinary Record, April 21, 1990.
    32. Jeffrey, M. and G. A. H. Wells, ``Spongiform Encephalopathy 
in a Nyala,'' Veterinary Pathology, 25:398-399, 1988.
    33. Kirkwood, J. K. et al, ``Spongiform Encephalopathy in an 
Arabian Oryx and a Greater Kudu,'' Veterinary Record, 127,17:418-
420, 1990.
    34. Wyatt, J. M. et al., ``Naturally Occurring Scrapie-like 
Spongiform Encephalopathy in Five Domestic Cats,'' Veterinary 
Record, 129:233-236, 1991.
    35. Leggett, M. M., J. Dukes, and H. M. Pirie, ``A Spongiform 
Encephalopathy in a Cat,'' Veterinary Record, 1990.
    36. Collee, J. G., ``Food Borne Illness--Bovine Spongiform 
Encephalopathy,'' Lancet, 336:1300-1303, 1990.
    37. Fraser, H. et al., ``Transmission of Bovine Spongiform 
Encephalopathy and Scrapie to Mice,'' Journal of General Virology, 
73:1891-1897, 1992.
    38. Robinson, M. M., ``Bovine Spongiform Encephalopathy,'' 
Foreign Animal Disease, pp. 134-138, 1992.
     39. USDA, APHIS, ``Qualitative Analysis of BSE Risk Factors in 
the United States,'' 1991.
    40. USDA, APHIS, ``Quantitative Risk Assessment of BSE in United 
States,'' 1991.
    41. Walker, K. D. et al, ``Comparison of Bovine Spongiform 
Encephalopathy Risk Factors in the United States and Great 
Britain,'' Journal of the American Veterinary Medical Association, 
199:11, 1554-1561, 1991.
    42. USDA, ``A Review of Bovine Spongiform Encephalopathy in 
Great Britain and an Update on Risk Factors for BSE in the United 
States,'' 1993.
    43. Wilesmith, J. W., ``The Epidemiology of Bovine Spongiform 
Encephalopathy,'' Seminars in Virology, 2:239-245, 1991.
    44. Office Internationale Epizootics, International Animal 
Health Code, chapter 3.2.13 on BSE, pp. 231-235, July 1993.
    45. USDA, Animal and Plant Health Inspection Service, Emergency 
Programs Activities, ``Bovine Spongiform Encephalopathy (BSE) 
Surveillance Program,'' in ``Foreign Animal Disease Report,'' No. 
20-3/4, pp. 1-2, 1992, and poster display at U.S. Animal Health 
Association annual meeting, October 30, 1993.
    46. Fancy, B., W. Hueston, A. Davis, A. Jenny, and L. Miller, 
``Retrospective Surveillance for Bovine Spongiform Encephalopathy 
(BSE) in the United States,'' in ``Animal Health Insight,'' pp. 11-
16, Winter 1991.
    47. Bisplinghoff, F. D., National Renderers Association letter 
to Animal Protein Producers, 1989.
    48. FDA, ``Report of Findings of Directed Inspections of Sheep 
Rendering Facilities,'' January 1993.
    49. Lamming, E., ``Bovine Spongiform Encephalopathy and Other 
Spongiform Encephalopathies,'' in ``The Report of the Expert Group 
on Animal Feedingstuffs to the Minister of Agriculture, Fisheries, 
and Food, the Secretary of State for Health and the Secretaries of 
State for Wales, Scotland, and Northern Ireland,'' 1992.

VII. Comments

    Interested persons may, on or before November 14, 1994, submit 
comments to the Dockets Management Branch (address above) written 
comments regarding this proposal. Two copies of any comments are to be 
submitted, except that individuals may submit one copy. Comments are to 
be identified with the docket number found in brackets in the heading 
of this document. Received comments may be seen in the office above 
between 9 a.m. and 4 p.m., Monday through Friday.

List of Subjects in 21 CFR Part 589

    Animal feeds, Animal foods, Food additives.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR part 589 be amended as follows:

PART 589--SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED

    1. The authority citation for 21 CFR part 589 continues to read as 
follows:

    Authority: Secs. 201, 402, 409, 701 of the Federal Food, Drug, 
and Cosmetic Act (21 U.S.C. 321, 342, 348, 371).

    2. New Sec. 589.2000 is added to subpart B to read as follows:


Sec. 589.2000  Specified offal from sheep and goats over 12 months old.

    (a) The Food and Drug Administration has determined that specified 
offal from sheep and goats over 12 months old is not generally 
recognized as safe for use in ruminant feed and is a food additive 
subject to section 409 of the Federal Food, Drug, and Cosmetic Act (the 
act). The Food and Drug Administration has determined that specified 
offal from sheep and goats over 12 months old is not prior sanctioned 
for use in ruminant feed. In the absence of a regulation providing for 
its safe use as a food additive under section 409 of the act, the use 
in ruminant feed of ingredients containing specified offal from sheep 
and goats over 12 months old causes the feed to be adulterated and in 
violation of the act, unless it is subject to an effective notice of 
claimed exemption for a food additive under Sec. 570.17 of this 
chapter.
    (b) For purposes of this part, the term ``specified offal'' means 
any tissue from the brain, spinal cord, spleen, thymus, tonsil, lymph 
nodes, or intestines (duodenum to anus, inclusive) of sheep or goats or 
any processed product that is reasonably expected to contain specified 
offal. Processed products that may contain specified offal include, but 
are not limited to, meat meal, meat and bone meal, animal byproduct 
meal, meat byproducts, glandular meal, and cooked bone meal.

    Dated: August 16, 1994.
Linda A. Suydam,
Interim Deputy Commissioner for Operations.
[FR Doc. 94-21278 Filed 8-26-94; 8:45 am]
BILLING CODE 4160-01-F